Systems and methods for performing variable sample preparation and analysis processes

Abstract

Apparatus and methods for analyzing samples, including for example, samples containing nucleic acids, antibodies, and/or antigens are described. The apparatus may include a frame having a cartridge receiver, two optical devices, thermal cycler, lysis assembly, hybridization heater, and sample transfer assembly. In use, the apparatus may perform multiple sample preparation and analysis processes within the same disposable cartridge including, for example, performing a PCR assay and immunoassay in the same cartridge.

We claim: 
     
       1. An apparatus, comprising:
 an instrument housing comprising a plurality of instrument bays, each of which is configured to hold a corresponding biological assay frame; 
 a biological assay control circuit configured to:
 receive, via a user interface, a request to perform a biological assay on at least one sample inserted into a particular biological assay frame within the instrument housing; and 
 instruct the particular biological assay frame to perform the request to perform the biological assay; and 
 output, via the user interface based on information received from the biological assay frame, results of the biological assay; 
 
 a plurality of electrical connectors configured to connect the biological assay control circuit to biological assay frames held within each of the plurality of instrument bays 
 a first biological assay frame disposed within a first instrument bay of the plurality of instrument bays; 
 a second biological assay frame disposed within a second instrument bay of the plurality of instrument bays; and 
 a third biological assay frame disposed within a third instrument bay of the plurality of instrument bays. 
 
     
     
       2. The apparatus of  claim 1 , wherein at least one of the first, second, and third biological assay frames comprises:
 an enclosure configured to receive a cartridge that includes a biological sample; 
 a first optical device configured to perform a first optical assay on a first region of the cartridge when the cartridge is disposed in the enclosure; 
 a second optical device configured to perform a second optical assay on a second region of the cartridge when the cartridge is disposed in the enclosure, wherein the second optical assay is a different type of optical assay than the first optical assay; and 
 an interface circuit configured to receive electronic instructions to use the first optical device to perform the first optical assay on a first subset of the biological sample, and to use the second optical device to perform a second optical assay on a second subset of the biological sample. 
 
     
     
       3. The apparatus of  claim 2 , wherein the at least one of the first, second, and third biological assay frames comprises: the enclosure configured to receive the cartridge that includes a biological sample; the second optical device configured to perform the second optical assay on the second region of the cartridge when the cartridge is disposed in the enclosure; and an interface circuit configured to receive electronic instructions to use the second optical device to perform an optical assay on the biological sample in the second region of the cartridge; wherein the at least one of the first, second, and third biological assay frames does not have the first optical device configured to perform the first optical assay on the first region of the cartridge when the cartridge is disposed in the enclosure. 
     
     
       4. A method for performing a multiplex biological assay comprising:
 inserting a cartridge that includes a biological sample into an apparatus according to  claim 2 ; 
 using the first optical device to perform a first optical assay on the biological sample in the first region of the cartridge; and 
 using the second optical device to perform a second optical assay on the biological sample, wherein the second optical assay is different from the first optical assay. 
 
     
     
       5. The method of  claim 4 , wherein: the first optical assay is a real time polymerase chain reaction performed on a first subset of a plurality of target nucleic acid sequences in the biological sample; and the second optical assay is an end-point analysis of a polymerase chain reaction performed on a second subset of the plurality of target nucleic acid sequences in the biological sample. 
     
     
       6. The method of  claim 5 , wherein the first subset of the target nucleic acid sequences comprises from one to six target nucleic acid sequences. 
     
     
       7. The method of  claim 5 , wherein the second subset of the target nucleic acid sequences comprises from one to thirty target nucleic acid sequences. 
     
     
       8. The method of  claim 5 , further comprising quantitating the amount of target nucleic acid sequences in the first subset of the target nucleic acid sequences. 
     
     
       9. A method for performing a multiplex biological assay comprising:
 inserting a cartridge that includes a biological sample comprising proteins and nucleic acids into an apparatus according to  claim 2 ; 
 transferring a first subset of the biological sample from a sample well of the cartridge to the first region of the cartridge; 
 transferring a second subset of the biological sample from the sample well of the cartridge to the second region of the cartridge; 
 using the first optical device to detect a polymerase chain reaction performed on the first subset of the biological sample in the first region of the cartridge; and 
 using the second optical device to detect an immunoassay performed on the second subset of the biological sample in the second region of the cartridge. 
 
     
     
       10. The apparatus of  claim 2 , wherein the first optical device comprises:
 a fluorimeter; and 
 a plurality of optical cables configured to transmit light between the fluorimeter and the first region of the cartridge when the cartridge is disposed in the enclosure. 
 
     
     
       11. The apparatus of  claim 2 , wherein the second optical device comprises:
 a light source configured to illuminate the second region when the cartridge is disposed in the enclosure; and 
 a detector configured to receive a light that is scattered or emitted from the second region when the cartridge is disposed in the enclosure. 
 
     
     
       12. The apparatus of  claim 2 , further comprising a thermal cycler configured to receive the first region of the cartridge. 
     
     
       13. The apparatus of  claim 12 , wherein the thermal cycler has one or more openings configured to receive one or more optical cables. 
     
     
       14. The method of  claim 4  wherein:
 the first optical assay is an optical analysis of a real-time PCR assay; and 
 the second optical assay is an optical analysis of a nucleic acid hybridization array assay. 
 
     
     
       15. The method of  claim 14  wherein the nucleic acid hybridization array assay comprises immobilized microspheres. 
     
     
       16. The method of  claim 15 , wherein the immobilized microspheres are fluorescently encoded microspheres immobilized on a surface of the second region. 
     
     
       17. The method of  claim 16 , wherein (i) the fluorescently encoded microspheres are magnetically responsive, (ii) the apparatus further comprises a magnet configured to produce a magnetic field in the second region of the cartridge when the cartridge is disposed in the enclosure, and (iii) the magnetic field immobilizes the fluorescently encoded microspheres on the surface of the second imaging region.